Syphilis is a chronic infection caused by the spirochete Treponema pallidum subsp. pallidum that is generally transmitted either through sexual contact or vertically from an infected mother to her fetus. Syphilis is a global health concern with an estimated burden of 25 million people worldwide and an estimated annual new incidence rate of 12 million cases. Further, infection with T. pallidum has been shown to increase the likelihood of contracting HIV. Congenital syphilis is recognized as the most significant disease affecting pregnancies and newborns worldwide, with over 2 million pregnant women estimated to be infected with syphilis every year. Without treatment, there are adverse outcomes in 69% of cases, including spontaneous abortion or stillbirth, neonatal complications, and infant mortality.
As a multi-stage disease, syphilis has historically been called the great imitator due to the similarity of its symptoms to other diseases. Primary syphilis is characterized by a painless open sore called a chancre, which develops on average 3 weeks after infection at the site of inoculation. The chancre spontaneously resolves, and 1-3 months later secondary symptoms may present. Secondary infection typically manifests as a generalized rash, often localizing to the trunk of the body, palms of the hands, and soles of the feet. After 1-3 months, secondary symptoms resolve and the disease enters an asymptomatic latent phase. In some instances the disease can progress from latency to a tertiary stage, which can involve the development of gummas, central nervous system complications or cardiovascular disease. Since the symptoms of syphilis infection are so similar to other diseases, and resolve on their own, syphilis has always been a challenging disease to diagnose clinically.
During primary infection when a chancre is present, dark-field microscopy and/or PCR can be performed to identify spirochetes present at the site of infection. The chancre normally resolves in 4-6 weeks, and often goes unnoticed if internally located in either the anus or vagina, making diagnosis by dark-field microscopy extremely limited.
Currently, there is no vaccine available to provide protection from T. pallidum. Thus, there is a need for therapies that can prevent or reduce the undesirable consequences of T. pallidum infection.